Substituted phenylguanidines and method

ABSTRACT

Phenylguanidine derivatives are provided having the structure ##STR1## wherein R is lower alkyl, cycloalkyl, cycloalkylalkyl, lower alkenyl, lower alkynyl, phenyl or benzyl; R 1  and R 2  may be the same or different and are lower alkyl or R 1  and R 2  may be taken together to form an alkylene linking group of 2 or 3 carbons or an o-phenylene group; R 3  and R 4  are the same or different and are lower alkyl, benzyl or phenyl; and n is 0 or 1. These compounds are useful as anthelmintic agents.

DESCRIPTION OF THE INVENTION

The present invention relates to phenylguanidine derivatives which areuseful as anthelmintic agents and have the structure ##STR2## wherein Ris lower alkyl, cycloalkyl, cycloalkylalkyl, lower alkenyl, loweralkynyl, phenyl, or benzyl; R¹ and R² may be the same or different andare lower alkyl or R¹ and R² taken together may form a cyclic-aliphaticimide (that is R¹ and R² represent an alkylene group of 2 or 3 carbons)or an aromatic imide (that is R¹ and R² are an o-phenylene moiety ring);R³ and R⁴ are the same or different and are lower alkyl, benzyl orphenyl; and n is 0 or 1.

The term "lower alkyl" or "alkyl" as used herein whether employed as anindependent substituent or as a part of another substituent includesstraight or branched chain aliphatic hydrocarbon radicals having up toand including 7 carbon atoms, preferably 1 to 3 carbons, such as methyl,ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, amyl, hexyl, heptyland the like.

The term "cycloalkyl" includes cyclic hydrocarbon groups containing 3 to12 carbons, which include cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, cyclooctyl, cyclodecyl and cyclododecyl, any ofwhich groups may be substituted with 1, 2, 3 or 4 halogen and/or 1, 2,3, or 4 lower alkyl groups.

The term "cycloalkylalkyl" refers to any of the above cycloalkyl groupslinked to a lower alkyl group as defined above.

The term "lower alkenyl" refers to an unsaturated hydrocarbon grouphaving from 3 to 6 carbon atoms and a single carbon-carbon double bond.Typical alkenyl groups include, for example, 2-propenyl, 1-propenyl,1-butenyl, 2-butenyl, 3-butenyl, and the like.

The term "lower alkynyl" refers to an unsaturated hydrocarbon grouphaving from 3 to 6 carbon atoms, and a single carbon-carbon triple bond.Typical alkynyl groups include, for example, 1-propynyl, 1-butynyl,2-propynyl, 2-butynyl, 3-butynyl, and the like.

Preferred are those compounds wherein R is lower alkyyl, R¹ and R²together form a 2 or 3 carbon alkylene chain, R³ and R⁴ are lower alkyland n is 0 or 1.

Thus, the compounds of the invention include the following: ##STR3##

The compounds of structure I may be prepared by reacting anilines of thestructure V ##STR4## with an S-methylisothiourea VI ##STR5## optionally,in the presence of an acid such as p-toluenesulfonic acid or aceticacid. The above reaction is preferably carried out at temperaturesranging from about 50° to about 100° C. for periods ranging from about 1to about 5 hours.

The aniline of structure V may be prepared by reduction of the nitroderivatives VII ##STR6## The reduction may be carried out catalyticallywith hydrogen and platinum or chemically with dithionite, or zinc and anacid such as hydrochloric acid or acetic acid.

The formula VII nitro derivatives are synthesized by reacting compoundsof the structure VIII ##STR7## with an appropriate reagent dependingupon the type of R¹, R² group to be present in the formula VII compound.Thus, diacylation of o-nitroanilines VIII using an acid anhydride IX,for example, acetic anhydride, in the presence of concentrated acid,such as, concentrated sulfuric acid will yield thediacyl-o-nitroanilines VII (J J. Blanksma, Chem. Z, 1909, II, 1219).

    (alkylCO).sub.2 O                                          (IX)

Reaction of VIII with acid anhydrides X, such as succinic anhydride,glutaric anhydride, or their corresponding di-acid chloride, will yieldimides XI ##STR8## while reaction of VIII with phthalic anhydride willyield the aromatic imide XII ##STR9##

Compounds of structures I, III and IV may also be prepared bycyclodehydrating acid derivatives ##STR10## wherein R⁵ is --(CH₂)_(m)CO₂ H or ##STR11##

Compounds of the structure VIII are prepared by reacting XIV ##STR12##with the appropriate thiol XV or preferably, the thiol salt to furnishVIII, where n is 0.

    R--S.sup.θ                                           XV

Compounds of structure VIII (n=0) can also be prepared by reducingthiocyanates XVI with sodium borohydride and then alkylating theresulting thiol XVII with the requisite halo-derivative RX. ##STR13##

The compounds of formula I wherein n is 1 may be prepared by oxidizingcompounds of formula I wherein n is 0, utilizing one equivalent of anoxidizing agent such as m-chloroperbenzoic acid, sodium m-periodate orhydrogen peroxide in acetic acid. Addition routes are outlined inHouben-Weyl's Methoden Der Organischen Chemie, Vol. 9, pp. 211-217(1955), C. Thieme Verlag, Stuttgart.

The oxidation step may also be introduced at an earlier stage in thereaction sequence. For example, nitro derivative VII where n is 0, ornitro derivative VIII where n is 0 may be oxidized with any of theaforementioned oxidizing agents to give VII or VIII, respectively,wherein n is 1.

The acid derivatives of structure XIII are prepared by reacting acompound of the structure VIII with a cyclic dicarboxylic acidanhydride, such as succinic anhydride or glutaric anhydride, or phthalicanhydride, in the presence of a strong acid, such as sulfuric acid andan aromatic solvent, such as toluene, benzene, chloroform or xylene,preferably at reflux, to form an acid of the structure XVIII or XIX##STR14## Refluxing solutions of XVIII or XIX in solvents such asbenzene or toluene will yield the cyclized products XI or XII.

In certain instances, the compounds of formula I form physiologicallyacceptable acidaddition salts with inorganic and organic acids. Thesesalts frequently provide useful means for isolating the products fromreaction mixtures by forming the salt in a medium in which it isinsoluble. The free base may then be obtained by neutralization. Thenany other salt may again be formed from the free base and theappropriate inorganic acid. Illustrative are the hydrohalides,especially the hydrochloride and hydrobromide which are preferred,sulfate, nitrate, tartrate, methanesulfonate, benzenesulfonate,toluenesulfonate, and the like.

The compounds of formula I have anthelmintic activity and are useful inthe treatment and/or prevention of helminthiasis, a parasitic diseasewhich causes widespread and often serious infection in domesticatedanimals such as swine, horses, cattle, dogs, cats and sheep. Thecompounds are useful in treating infections caused by Haemonchus,Ostertagia, Trichostrongylus, Cooperia, Dictyocaulus, Nematodirus,Bunostomum, Strongyloides, Oesophagostomum, Trichuris, Moniezia, andliver flukes (for example in sheep). In treating domesticated animals,the compounds are given orally; however, other routes such asparenterally, for example, subcutaneously, intravenously,interperitoneally and intramuscularly may be employed.

Where the compounds are administered orally, they may be mixed with anontoxic, edible carrier to form a feed supplement, or may beadministered in unit dosage forms such as powders, capsule, tablet,boluses, drenches, etc.

Where the compounds are administered parenterally, they may be dispersed(for example, suspended) in non-toxic non-pyrogenic physiologicallyacceptable carriers such as water, benzyl benzoate, 1,3-butylene glycol,ethyl oleate, glyceryl triacetate, castor oil, sesame oil, and sesameoil:benzyl benzoate (1:1). The parenteral product will usually take theform of a suspension containing from about 1 to about 10% by weight ofthe compound of formula I in anyone or mixture of the above carriers.

In general, the compounds of formula I exhibit anthelmintic activitywhen administered to animals (parenterally or orally) in a single doseof about 1 to about 100 mg per kilogram of animal body weight. It ispreferred to employ in the range of 2.5-25 mg per kilogram of bodyweight. The compounds may be divided into a plurality of smaller dosesgiven parenterally or orally over one or more days.

When the compounds of formula I are to be administered in unit dosageform, capsules, boluses or drenches containing the desired amount ofanthelmintic distributed in a pharmaceutically acceptable vehicle areusually employed. These are prepared by intimately and uniformly mixingthe active ingredient with suitable finely divided diluents, suspendingagents, fillers, disintegrating agents and/or binders such as starch,lactose, talc, magnesium stearate, vegetable gums and the like and arecompounded by techniques generally known in the art.

The compounds of formula I may also be administered as a component ofthe feed of the animals or suspended in the drinking water. Thus, novelfeed and feed supplement compositions may be prepared in which thecompounds of this invention are present as an active anthelminticingredient. A typical feed supplement comprises the anthelmintic agentintimately dispersed in or admixed with an inert carrier or diluent,i.e., one that is nonreactive with respect to the anthelmintic agent andthat may be administered with safety to the animals. The carrier ordiluent is preferably one that is or may be an ingredient of an animalration. This composition may be mixed with the feed to give any usefuldesired concentration, preferably about 0.1-2%. Lastly, feeds containingthe active ingredient may be made directly by mixing said activeingredient in a feed which is inert to said anthelmintic compounds so asto give feeds having concentrations of anthelmintic agent of from0.1-2%.

The following examples are provided for illustrative purposes and mayinclude particular features of the invention, however the examplesshould not be construed as limiting the invention, many variations ofwhich are possible without departing from the spirit or scope thereof.All temperatures are in degrees centigrade.

EXAMPLE 14-[[2-[[[(Methoxycarbonyl)amino][(methoxycarbonyl)-imino]methyl]amino]-5-[(1-methylpropyl)thio]phenyl]amino]-4-oxobutanicacid A. [[(Methoxycarbonyl)amino](methylthio)-methylene]carbamic acid,methyl ester

To a solution of 112 g of S-methyl-2-thiourea sulfate in 200 ml of waterat 0° C. there is added concurrently 260 ml of 25% NaOH and 160 ml ofmethyl chloroformate at such a rate that the pH remains between 7 and 8as monitored by a pH meter. After the addition is complete the mixtureis stirred for an additional 2 hours at room temperature. Then 400 ml ofwater is added and the mixture is extracted with dichloromethane. Theorganic layers are combined, dried over magnesium sulfate, andevaporated in vacuo to give a white solid. Crystallization from methanolyields 60.4 g, m.p. 99°-101° C.

B.4-[[2-[[[Methoxycarbonyl)amino][(methoxycarbonyl)imino]methyl]amino]-5-[(1-methylpropyl)thio]phenyl]amino]-4-oxobutanicacid

A mixture of 11.2 g (0.05 mole) of5-[(2-methylpropyl)thio]-2-nitroaniline, 5.0 g of succinic anhydride and0.5 ml of H₂ SO₄ is refluxed in 100 ml of toluene for 1 hour. Themixture is fitered off and evaporated in vacuo. The residue iscrystallized from Et₂ O to yield 7.5 g, m.p. 135°-140° C.

A mixture of 6.0 g (0.02 mole) of the above nitro compound and 0.6 g ofPtO₂ in 200 ml of absolute ethanol is reduced on the Parr hydrogenatorat 50 psi until the theoretical amount of hydrogen is absorbed. Themixture is filtered and the solvent is removed in vacuo to leave an oilwhich is used immediately in the following reaction.

To a solution of the above amine in 200 ml of methanol there is added4.0 g (0.02 mole) of[[(methoxycarbonyl)amino](methylthio)methylene]-carbamic acid, methylester and 1 ml of acetic acid and the mixture is refluxed for 3 hours.The reaction mixture is filtered hot, reduced in volume in vacuo andcooled. The resulting solid is filtered off, washed with Et₂ O, andcrystallized from EtOH to yield 0.9 g, m.p. 166°-168° C.

EXAMPLE 2[[[2-(2,5-Dioxo-1-pyrrolidinyl)-4-[(1-methylpropyl)-thio]phenyl]amino][(methoxycarbonyl)amino]methyl]-carbamicacid, methyl ester

A mixture of 11.2 g (0.05 mole) of5-[(2-methylpropyl)thio]-2-nitroaniline and 5.0 g of succinic anhydrideis refluxed in 100 ml of benzene for 1 hour. The mixture is filtered andthe solvent is removed in vacuo. The residue is crystallized from Et₂ Oto yield 11.1 g, m.p. 98°-100° C.

A mixture of 9.0 g (0.03 mole) of the above nitro compound and 1.0 g ofPtO₂ in 200 ml of absolute ethanol is reduced on the Parr hydrogenatorat 50 psi until the theoretical amount of hydrogen is absorbed. Themixture is filtered and the solvent is removed in vacuo to leave an oilwhich is used immediately in the following reaction.

To a solution of the above amine in 200 ml of methanol there is added6.0 g (0.03 mole) of[[(methoxycarbonyl)amino](methylthio)methylene]-carbamic acid, methylester and 1 ml of acetic acid and the mixture is refluxed for 3 hours.The reaction mixture is filtered hot, reduced in volume in vacuo and Et₂O is added. On standing, crystals which separate are filtered off toyield 2.1 g, m.p. 138°-140° C.

EXAMPLE 3[[[2-(2,5-Dioxo-1-pyrrolidinyl)-4-[(1-methylpropyl)-sulfinyl]phenyl]amino][(methoxycarbonyl)amino]methyl]carbamicacid, methyl ester

To a solution of 3.9 g (0.01 mole) of[[[2-(2,5-dioxo-1-pyrrolidinyl)-4-[(2-methylpropyl)-thio]phenyl]amino][(methoxycarbonyl)amino]methylene]carbamicacid, methyl ester in 250 ml of chloroform there is added 2.0 g (0.01mole) of 85% m-chloroperoxybenzoic acid in 10 ml of chloroform with icebath cooling. The reaction mixture is allowed to warm to roomtemperature and then stirred for 3 hours. The reaction mixture is washedwith aqueous potassium carbonate and then with water until the pH is 7.The organic layer is dried (MgSO₄), filtered, and evaporated in vacuo.The residue is crystallized from ethanol to yield the title compound.

EXAMPLE 4[[[2-(N,N-Diacetylamino)-4-[(1-methylpropyl)-thio]phenyl]amino][(methoxycarbonyl)amino]methyl]carbamicacid, methyl ester

To 5 g of 2-nitro-5(2-methylpropyl)thio aniline, there is added 50 ml ofacetic anhydride and several drops of concentrated sulfuric acid. Themixture is refluxed for several hours, the excess acetic anhydrideevaporated, and the resulting residue is crystallized to furnish2-nitro-5-(2-methylpropyl)thio-N,N-diacetyl aniline.

A mixture of 9.0 g (0.03 mole) of the above nitro compound and 1.0 g ofPtO₂ in 200 ml of absolute ethanol is reduced on the Parr hydrogenatorat 50 psi until the theoretical amount of hydrogen is absorbed. Themixture is filtered and the solvent is removed in vacuo to leave an oilwhich is used immediately in the following reaction.

To a solution of the above amine in 200 ml of methanol there is added6.0 g (0.03 mole) of[[(methoxycarbonyl)amino](methylthio)methylene]-carbamic acid, methylester and 1 ml of acetic acid and the mixture is refluxed for 3 hours.The reaction mixture is filtered hot, reduced in volume in vacuo and Et₂O is added. On standing, the title compound crystallizes.

EXAMPLE 5[[[2-(N,N-Diacetylamino)-5-[(2-methylpropyl)-sulfinyl]phenyl]amino][(methoxycarbonyl)amino]-methyl]carbamicacid, methyl ester

To a solution of 3.9 g (0.01 mole) of[[[2-(N,N-diacetylamino)-4-[(1-methylpropyl)thio]phenyl]amino][methoxycarbonyl)amino]methyl]carbamicacid, methyl ester in 250 ml of chloroform there is added 2.0 g (0.01mole) of 85% m-chloroperoxybenzoic acid in 10 ml of chloroform with icebath cooling. The reaction mixture is allowed to warm to roomtemperature and then stirred for 3 hours. The reaction mixture is washedwith aqueous potassium carbonate and then with water until the pH is 7.The organic layer is dried (MgSO₄), filtered, and evaporated in vacuo.The residue is crystallized from ethanol to yield the title compound.

EXAMPLES 6 to 21

Following the procedure of Examples 1 and 2 but substituting for5-[(2-methylpropyl)thio]-2-nitroaniline, the aniline derivative shown inColumn I of Table I set out below, substituting for succinic anhydride,the compound shown in Column II, and substituting for[[(methoxycarbonyl)-amino](methylthio)methyl]carbamic acid, methylester, the compound shown in Column III, the product in accordance withthe present invention shown in Column IV is obtained.

                                      TABLE I                                     __________________________________________________________________________    Column I         Column II Column III  Column IV                               ##STR15##                                                                                      ##STR16##                                                                               ##STR17##                                                                                 ##STR18##                             Ex.                                          (position                        No.                                                                              R (position of RS)                                                                          R.sup.1                                                                            R.sup.2                                                                            R.sup.3                                                                             R.sup.4                                                                             R     of RS)                                                                              R.sup.1                                                                          R.sup.                                                                           R.sup.3                                                                          R.sup.4           __________________________________________________________________________                                           .BHorizBrace.                                                                             .BHorizBrace.                                                                       .BHorizBrace.        6. (CH.sub.3).sub.2 CHCH.sub.2 (5)                                                             CH.sub.2 CH.sub.2                                                                       CH.sub.3                                                                            CH.sub.3                                                                            as in (4)   as in as in                    ##STR19##    CH.sub.2 CH.sub.2 CH.sub.2                                                              CH.sub.3                                                                            CH.sub.3                                                                            Column I                                                                            (4)   Column                                                                              Column III           8. CH.sub.2CHCH.sub.2 (5)                                                                       ##STR20##                                                                              C.sub.6 H.sub.5                                                                     C.sub.6 H.sub.5                                                                           (4)                              9. (CH.sub.3).sub.2 CH (5)                                                                     CH.sub.2 CH.sub.2                                                                       CH.sub.3                                                                            CH.sub.3    (4)                              10.                                                                              CHCCH.sub.2(4)                                                                              CH.sub.2 CH.sub.2                                                                       CH.sub.2 C.sub.6 H.sub.5                                                            CH.sub.2 C.sub.6 H.sub.5                                                                  (5)                                  ##STR21##    CH.sub.2 CH.sub.2 CH.sub.2                                                              C.sub.2 H.sub.5                                                                     C.sub.2 H.sub.5                                                                           (4)                                  ##STR22##    CH.sub.2 CH.sub.2                                                                       CH.sub.3                                                                            CH.sub.3    (4)                                 C.sub.6 H.sub.5 CH.sub.2 (4)                                                                CH.sub.2 CH.sub.2                                                                       CH.sub.3                                                                            CH.sub.3    (5)                                  ##STR23##                                                                                   ##STR24##                                                                              C.sub.2 H.sub.5                                                                     C.sub.2 H.sub.5                                                                           (4)                                 (CH.sub.3).sub.2 CH(5)                                                                      CH.sub.2 CH.sub.2 CH.sub.2                                                              C.sub.6 H.sub.5                                                                     C.sub.6 H.sub.5                                                                           (4)                                 (CH.sub.3).sub.2 CHCH.sub.2(5)                                                               ##STR25##                                                                              CH.sub.3                                                                            CH.sub.3    (4)                                  ##STR26##    CH.sub.2 CH.sub.2 CH.sub.2                                                              CH.sub.3                                                                            CH.sub.3    (4)                                 CH.sub.2CHCH.sub.2 (5)                                                                      CH.sub.2 CH.sub.2                                                                       C.sub.6 H.sub.5                                                                     C.sub.6 H.sub.5                                                                           (4)                                  ##STR27##    CH.sub.2 CH.sub.2                                                                       CH.sub.3                                                                            CH.sub.3    (4)                              20.                                                                              C.sub.6 H.sub. 5 (5)                                                                        CH.sub.2 CH.sub.2                                                                       CH.sub.3                                                                            CH.sub.3    (4)                                 CH.sub.2CHCH.sub.2 (5)                                                                      CH.sub.2 CH.sub.2                                                                       CH.sub.2 C.sub.6 H.sub.5                                                            CH.sub.2 C.sub.6 H.sub.5                                                                  (4)                              __________________________________________________________________________

EXAMPLES 22 TO 31

Following the procedure of Example 4, but substituting for2-nitro-5-(2-methylpropyl)-thioaniline, the aniline derivative shown inColumn I of Table II set out below, substituting for acetic anhydride,the compound shown in Column II, and substituting for[[(methoxycarbonyl)amino]-(methylthio)methyl]carbamic acid, methylester, the compound shown in Column III, the product in accordance withthe present invention shown in Column IV is obtained.

                                      TABLE II                                    __________________________________________________________________________    Column I        Column II                                                                              Column III                                                                               Column IV                                  ##STR28##       (alkylCO).sub.2 O                                                                      ##STR29##                                                                               ##STR30##                                 Ex.                                     (position                             No.                                                                              R(position of RS)                                                                          alkyl    R.sup.3                                                                            R.sup.4                                                                            R    of RS)                                                                             alkyl   R.sup.3                                                                            R.sup.4             __________________________________________________________________________                                      .BHorizBrace.                                                                            .BHorizBrace.                                                                         .BHorizBrace.               i-C.sub.3 H.sub.7 (5)                                                                      CH.sub.3 CH.sub.3                                                                           CH.sub.3                                                                          as in (4)  as in Column                                                                          as in                        ##STR31##   C.sub.2 H.sub.5                                                                        C.sub.2 H.sub.5                                                                    C.sub.2 H.sub.5                                                                   Column I                                                                            (4)          Column III                  CH.sub.2CHCH.sub.2 (5)                                                                     CH.sub.3 CH.sub.3                                                                           CH.sub.3  (4)                                      (CH.sub.3).sub.2 CHCH.sub.2 (5)                                                            C.sub.2 H.sub.5                                                                        CH.sub.2 C.sub.6 H.sub.5                                                           CH.sub.2 C.sub.6 H.sub.5                                                                (4)                                      CHCCH.sub.2 (4)                                                                            n-C.sub.3 H.sub.7                                                                      C.sub.6 H.sub.5                                                                    C.sub.6 H.sub.5                                                                         (5)                                       ##STR32##   n-C.sub.4 H.sub.9                                                                      CH.sub.3                                                                           CH.sub.3  (4)                                       ##STR33##   C.sub.5 H.sub.11                                                                       C.sub.2 H.sub.5                                                                    C.sub.2 H.sub.5                                                                         (4)                                      C.sub.6 H.sub.5 CH.sub.2 (4)                                                               CH.sub.3 CH.sub.3                                                                           CH.sub.3  (5)                                   30.                                                                               ##STR34##   C.sub.2 H.sub.5                                                                        CH.sub.3                                                                           CH.sub.3  (4)                                      C.sub.6 H.sub.5 (5)                                                                        i-C.sub.3 H.sub.7                                                                      C.sub.2 H.sub.5                                                                    C.sub.2 H.sub.5                                                                         (4)                                   __________________________________________________________________________

EXAMPLES 32 TO 57

Following the procedure of Example 3 except substituting the compoundsof Examples 6 to 31 for the[[[2-(2,5-dioxo-1-pyrrolidinyl)-4-[(1-methylpropyl)thio]phenyl]amino][methoxycarbonyl)amino]methyl]carbamicacid, methyl ester, the corresponding sulfoxides of the compounds ofExamples 6 to 31 are obtained.

What is claimed is:
 1. A compound of the structure ##STR35## wherein Ris lower alkyl, cycloalkyl having 3 to 12 carbons, cycloalkyl-loweralkyl having 3 to 12 carbons in the cycloalkyl portion, lower alkenyl,lower alkynyl, phenyl or benzyl, R¹ and R² may be the same or differentand are lower alkyl of R¹ and R² taken together may form an alkylenelinking group of 2 or 3 carbons or an o-phenylene group; R³ and R⁴ arethe same or different and are lower alkyl, benzyl or phenyl, and n is 0or 1, and physiologically acceptable salts thereof.
 2. The compound asdefined in claim 1 wherein n is
 0. 3. The compound as defined in claim 1wherein n is
 1. 4. The compound as defined in claim 1 wherein R¹ islower alkyl and R² is lower alkyl.
 5. The compound as defined in claim 1having the structure ##STR36## wherein m is 2 or
 3. 6. The compound asdefined in claim 1 having the structure ##STR37##
 7. The compound asdefined in claim 1 wherein R is lower alkyl, R¹ and R² are takentogether to form (CH₂)₂ or (CH₂)₃, and R³ and R⁴ are lower alkyl.
 8. Thecompound as defined in claim 1 having the name[[[2-(2,5-dioxo-1-pyrrolidinyl)-4-[(1-methylpropyl)thio]phenyl]amino][(methoxycarbonyl)amino]methyl]carbamicacid, methyl ester.
 9. The compound as defined in claim 1 having thename[[[2-(2,5-dioxo-1-pyrrolidinyl)-4-[(1-methylpropyl)sulfinyl]phenyl]amino][(methoxycarbonyl)amino]methyl]carbamicacid, methyl ester.
 10. An anthelmintic composition comprising atherapeutic amount of a compound as defined in claim 1 and apharmaceutically acceptable carrier therefor.
 11. A method for treatingor preventing helminth infestation in mammalian hosts which comprisesadministering to a mammal a therapeutic amount of an anthelminticcomposition as defined in claim
 10. 12. The method as defined in claim11 wherein said composition is administered orally or parenterally. 13.The method as defined in claim 12 wherein said composition isadministered parenterally.